CXCL10+ peripheral activation niches couple preferred sites of Th1 entry with optimal APC encounter
Summary: Correct positioning of T cells within infected tissues is critical for T cell activation and pathogen control. Upon tissue entry, effector T cells must efficiently locate antigen-presenting cells (APC) for peripheral activation. We reveal that tissue entry and initial peripheral activation...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-08-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124721009542 |
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doaj-0a85c8030eb34cd78c988f80a522b72a |
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Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Hen Prizant Nilesh Patil Seble Negatu Noor Bala Alexander McGurk Scott A. Leddon Angela Hughson Tristan D. McRae Yu-Rong Gao Alexandra M. Livingstone Joanna R. Groom Andrew D. Luster Deborah J. Fowell |
| spellingShingle |
Hen Prizant Nilesh Patil Seble Negatu Noor Bala Alexander McGurk Scott A. Leddon Angela Hughson Tristan D. McRae Yu-Rong Gao Alexandra M. Livingstone Joanna R. Groom Andrew D. Luster Deborah J. Fowell CXCL10+ peripheral activation niches couple preferred sites of Th1 entry with optimal APC encounter Cell Reports CD4 T cells Th1 chemokine CXCL10 CXCR3 inflammation |
| author_facet |
Hen Prizant Nilesh Patil Seble Negatu Noor Bala Alexander McGurk Scott A. Leddon Angela Hughson Tristan D. McRae Yu-Rong Gao Alexandra M. Livingstone Joanna R. Groom Andrew D. Luster Deborah J. Fowell |
| author_sort |
Hen Prizant |
| title |
CXCL10+ peripheral activation niches couple preferred sites of Th1 entry with optimal APC encounter |
| title_short |
CXCL10+ peripheral activation niches couple preferred sites of Th1 entry with optimal APC encounter |
| title_full |
CXCL10+ peripheral activation niches couple preferred sites of Th1 entry with optimal APC encounter |
| title_fullStr |
CXCL10+ peripheral activation niches couple preferred sites of Th1 entry with optimal APC encounter |
| title_full_unstemmed |
CXCL10+ peripheral activation niches couple preferred sites of Th1 entry with optimal APC encounter |
| title_sort |
cxcl10+ peripheral activation niches couple preferred sites of th1 entry with optimal apc encounter |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2021-08-01 |
| description |
Summary: Correct positioning of T cells within infected tissues is critical for T cell activation and pathogen control. Upon tissue entry, effector T cells must efficiently locate antigen-presenting cells (APC) for peripheral activation. We reveal that tissue entry and initial peripheral activation of Th1 effector T cells are tightly linked to perivascular positioning of chemokine-expressing APCs. Dermal inflammation induces tissue-wide de novo generation of discrete perivascular CXCL10+ cell clusters, enriched for CD11c+MHC-II+ monocyte-derived dendritic cells. These chemokine clusters are “hotspots” for both Th1 extravasation and activation in the inflamed skin. CXCR3-dependent Th1 localization to the cluster micro-environment prolongs T-APC interactions and boosts function. Both the frequency and range of these clusters are enhanced via a T helper 1 (Th1)-intrinsic, interferon-gamma (IFNγ)-dependent positive-feedback loop. Thus, the perivascular CXCL10+ clusters act as initial peripheral activation niches, optimizing controlled activation broadly throughout the tissue by coupling Th1 tissue entry with enhanced opportunities for Th1-APC encounter. |
| topic |
CD4 T cells Th1 chemokine CXCL10 CXCR3 inflammation |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124721009542 |
| work_keys_str_mv |
AT henprizant cxcl10peripheralactivationnichescouplepreferredsitesofth1entrywithoptimalapcencounter AT nileshpatil cxcl10peripheralactivationnichescouplepreferredsitesofth1entrywithoptimalapcencounter AT seblenegatu cxcl10peripheralactivationnichescouplepreferredsitesofth1entrywithoptimalapcencounter AT noorbala cxcl10peripheralactivationnichescouplepreferredsitesofth1entrywithoptimalapcencounter AT alexandermcgurk cxcl10peripheralactivationnichescouplepreferredsitesofth1entrywithoptimalapcencounter AT scottaleddon cxcl10peripheralactivationnichescouplepreferredsitesofth1entrywithoptimalapcencounter AT angelahughson cxcl10peripheralactivationnichescouplepreferredsitesofth1entrywithoptimalapcencounter AT tristandmcrae cxcl10peripheralactivationnichescouplepreferredsitesofth1entrywithoptimalapcencounter AT yuronggao cxcl10peripheralactivationnichescouplepreferredsitesofth1entrywithoptimalapcencounter AT alexandramlivingstone cxcl10peripheralactivationnichescouplepreferredsitesofth1entrywithoptimalapcencounter AT joannargroom cxcl10peripheralactivationnichescouplepreferredsitesofth1entrywithoptimalapcencounter AT andrewdluster cxcl10peripheralactivationnichescouplepreferredsitesofth1entrywithoptimalapcencounter AT deborahjfowell cxcl10peripheralactivationnichescouplepreferredsitesofth1entrywithoptimalapcencounter |
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doaj-0a85c8030eb34cd78c988f80a522b72a2021-08-12T04:33:58ZengElsevierCell Reports2211-12472021-08-01366109523CXCL10+ peripheral activation niches couple preferred sites of Th1 entry with optimal APC encounterHen Prizant0Nilesh Patil1Seble Negatu2Noor Bala3Alexander McGurk4Scott A. Leddon5Angela Hughson6Tristan D. McRae7Yu-Rong Gao8Alexandra M. Livingstone9Joanna R. Groom10Andrew D. Luster11Deborah J. Fowell12David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USADavid H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USADavid H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USADavid H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USA; Department of Microbiology and Immunology, Cornell University, Ithaca, NY, USADavid H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USA; Department of Microbiology and Immunology, Cornell University, Ithaca, NY, USADavid H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USA; Department of Microbiology and Immunology, Cornell University, Ithaca, NY, USADavid H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USADepartment of Neuroscience and Multiphoton and Analytical Imaging Center, University of Rochester Medical Center, Rochester, NY, USADepartment of Neuroscience and Multiphoton and Analytical Imaging Center, University of Rochester Medical Center, Rochester, NY, USADavid H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USAWalter and Eliza Hall Institute of Medical Research, Melbourne, VIC, AustraliaCenter for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USADavid H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USA; Department of Microbiology and Immunology, Cornell University, Ithaca, NY, USA; Corresponding authorSummary: Correct positioning of T cells within infected tissues is critical for T cell activation and pathogen control. Upon tissue entry, effector T cells must efficiently locate antigen-presenting cells (APC) for peripheral activation. We reveal that tissue entry and initial peripheral activation of Th1 effector T cells are tightly linked to perivascular positioning of chemokine-expressing APCs. Dermal inflammation induces tissue-wide de novo generation of discrete perivascular CXCL10+ cell clusters, enriched for CD11c+MHC-II+ monocyte-derived dendritic cells. These chemokine clusters are “hotspots” for both Th1 extravasation and activation in the inflamed skin. CXCR3-dependent Th1 localization to the cluster micro-environment prolongs T-APC interactions and boosts function. Both the frequency and range of these clusters are enhanced via a T helper 1 (Th1)-intrinsic, interferon-gamma (IFNγ)-dependent positive-feedback loop. Thus, the perivascular CXCL10+ clusters act as initial peripheral activation niches, optimizing controlled activation broadly throughout the tissue by coupling Th1 tissue entry with enhanced opportunities for Th1-APC encounter.http://www.sciencedirect.com/science/article/pii/S2211124721009542CD4 T cellsTh1chemokineCXCL10CXCR3inflammation |